High-grade Endometrial Stromal Sarcoma Research Articles

Exploring Immunohistochemical Profiling in High-Grade Endometrial Stromal Sarcoma - A Case Study

Abstract Introduction/Objective High grade endometrial stromal sarcoma (HGESS) is a rare and aggressive tumor of endometrial stromal origin comprising about 0.2% of all uterine malignancies. It is often misdiagnosed preoperatively as uterine leiomyoma, leiomyosarcoma or endometrial carcinoma due to lack of well defined clinical and radiological features. We present an unusual case of HGESS with fibroid uterus and abnormal vaginal bleeding. Methods/Case Report A 73-year-old female with a past medical history of uterine fibroids presented with abnormal vaginal bleeding for 6 months. Her MRI uterus revealed enlarged uterus measuring 6.8 X 9.9 X 9.3 cm, multiple fibroids, and endometrial thickness of 4 mm. Hysteroscopic dilation and curettage revealed endometrial polyp and submucosal fibroid. Histopathology of submucosal fibroid revealed loosely cohesive tumor cells with high nuclear/cytoplasmic ratio, scant cytoplasm, and large prominent nucleoli, arranged in solid sheets with myxoid stroma. No glandular formation was identified. Tumor cell necrosis, bizarre tumor cells, and markedly increased mitotic activity, including atypical mitotic figures were present. Immunohistochemistry (IHC) revealed tumor cells diffusely positive for smooth muscle actin, CD10, p53, negative for AE1/AE3, CK7, cam5.2, EMA, ER, PR, desmin, and caldesmon. Ki-67 labels close to 50% of the tumor cells. Combined morphologic and IHC features favored the diagnosis of high-grade sarcoma, including leiomyosarcoma and HGESS. However, the possibility of carcinosarcoma (CS) could not be ruled out. Patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Final histopathological diagnosis revealed HGESS, pT1b. Lack of carcinomatous component and negative IHC staining for CK7, CAM 5.2, AE1/AE3 ruled out CS. IHC showed tumor cells diffusely positive for CD10, actin, desmin and CD 56, focally positive for caldesmon, cyclin D1 and CD 117 and negative for DOG 1, further supporting the diagnosis for HGESS over leiomyosarcoma. Results (if a Case Study enter NA) NA Conclusion Definitive diagnosis of HGESS is achieved through histology and IHC. An appropriate panel of IHC markers is essential to differentiate between endometrial stromal tumors from leiomyosarcoma and CS. Accurate diagnose of this rare clinical entity is critical especially in its initial stages owing to its poor prognosis and aggressive nature.

Survival Trends for Uterine Sarcomas from a Tertiary Center: The Oxford Experience.

Uterine sarcomas are rare and aggressive gynecological malignancies. We evaluated the epidemiology, treatment outcomes and survival rates in uterine sarcoma patients managed in our institute. The medical records of women with histology proven uterine sarcoma, including leiomyosarcoma (LMS), adenosarcoma (ADS), and endometrial stromal sarcoma (ESS), treated at our institution from February 2010 to February 2022, were analyzed. In total, 41 patients were identified. In detail, LMS, ADS, and high-grade and low-grade ESS were identified, respectively, in 60.9%, 19.5%, 12.1%, and 7.3% of the cases. The majority of women affected by LMS (72%) underwent primary surgery and 40% of them also received adjuvant chemotherapy. A surgical approach was the preferred mode of treatment in 83% of the recurrences. The median OS (overall survival), DFS (disease free survival), and PFS (progression free survival) for the LMS group were 25, 44.5, and 8 months, respectively. The 5-year survival rates for LMS, ADS, and ESS groups were 30.5%, 100% and 37.5%, respectively. The 5-year survival for LMS was found to be significantly worse than for other histology types (p = 0.016). Our study provides valuable data for the evaluation of treatment strategies and survival trends among these rare cancers. The management and follow-up planning of each subtype requires a thorough patient-focused multidisciplinary discussion.

Prognostic Factors in Uterine Sarcoma Based on the Tumor Size Stratification: A Retrospective Study.

Uterine sarcoma is a rare malignant gynecological tumor with a poor prognosis. Many studies have identified the clinical stage as an important prognostic factor; however, the heterogeneity of patient distribution in the International Federation of Gynecology and Obstetrics (FIGO) stage has reportedly required further revision. Therefore, this study retrospectively investigated the factors related to the prognosis of uterine sarcoma, with particular attention to tumor size, which can be evaluated preoperatively. Clinical data were extracted from the medical records of patients with uterine sarcoma treated between January 2010 and January 2023. Kaplan-Meier survival curves were plotted according to clinical factors such as histological type, clinical stage, chemotherapy, and tumor size. Factors that were significant in the univariate analysis were subjected to the multivariate analysis using Cox proportional hazards regression. Thirty-four patients with uterine sarcoma, comprising 24 (70.5%), five (14.7%), three (8.8%), and two (5.9%) with leiomyosarcoma, undifferentiated sarcoma, high-grade endometrial stromal sarcoma, and low-grade endometrial stromal sarcoma, respectively, were included. Based on the FIGO stage, 15 (44.1%), six (17.6%), three (8.8%), and 10 patients had stage I, II, III, and IV disease, respectively, at the time of diagnosis. All patients underwent surgery as initial treatment; 15 received postoperative chemotherapy. Among the 32 patients with uterine leiomyosarcoma, undifferentiated sarcoma, or high-grade endometrial stromal sarcoma, overall survival differed significantly in the univariate analysis based on disease stage (I + II vs. III + IV) and tumor size (≤10 vs. >10 cm). However, only tumor size was an independent prognostic factor in the multivariate analysis. Tumor size (≤10 vs. >10 cm) may possibly have a prognostic impact on uterine sarcoma.

ATM, BLM, and CDH1 gene co-mutations in a high-grade endometrial stromal sarcoma patient with multiple abdominal cavity metastases: a case report and literature review

BackgroundHigh-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed.Case presentationA 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib.ConclusionsDue to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS.

Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas.

The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the USs. Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), 3 adenosarcomas, 2 carcinosarcomas, and 1 uterine tumor resembling an ovarian sex-cord tumor (UTROSCT). ESS (including high-grade ESS and low-grade ESS) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A - PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uDEGs were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named MMN-MIL showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Diagnostic Value of Combined BCOR, Cyclin D1, and CD10 in Differentiating Endometrial Stromal Sarcoma From Other Uterine Spindle Cell Lesions.

Uterine spindle cell lesions share a dilemmatic overlapped features that needed to be addressed by the pathologist to reach a conclusive accurate diagnosis for its prognostic value and different management decisions. Usage of combined IHC panel can be an aiding guiding tool in this context. The aim of this study is to evaluate the diagnostic value of combined BCOR, Cyclin D1, and CD10 IHC panel in differentiating endometrial stromal sarcoma from other uterine spindle cell lesions. This study included 60 cases categorized into endometrial stromal sarcoma group (ESS) (12 cases high-grade endometrial stromal sarcoma [HGESS] and 18 cases low-grade endometrial stromal sarcoma [LGESS]), malignant uterine spindle cell lesions group (5 cases adenosarcoma [AS], 6 cases leiomyosarcoma [LS], 4 cases carcinosarcoma [CS]), and benign uterine lesions group (5 cases endometrial stromal nodule [ESN], 5 cases leiomyoma, and 5 cases adenomyosis). IHC staining procedure and evaluation for BCOR, Cyclin D1, and CD10 was performed on all studied cases. BCOR IHC staining was positive in all HGESS (12/12) of ESS group cases, with diffuse pattern in 75% of cases. BCOR-diffuse staining pattern was not recorded in any of LGESS (0/18), malignant mesenchymal lesions group (0/15), and also benign lesions group (0/15). Cyclin D1 positivity was observed only in HGESS cases, in parallel with positive-BCOR expression. On the contrary, CD10 was negatively expressed in all HGESS and positive in all LGESS, ESN, and adenomyosis cases. A specificity of 100% and sensitivity of 75% were recorded in differentiating HGESS from malignant mesenchymal lesions (including LMS, AS, and CS) and also HGESS from LGESS when using the combined panel BCOR +ve D /Cyclin D1 +ve / CD10 -ve , considering only the BCOR-diffuse staining pattern. In conclusion, BCOR +ve D /Cyclin D1 +ve /CD10 -ve as a combined panel is 100% specific and with lesser sensitivity in diagnosing HGESS as well as differentiating it from LGESS and other malignant uterine spindle cell lesions.

Exploring the Clinicopathological Diversity in Sarcomatous Transformations in the Uterus.

Introduction Uterine sarcomas are a rare group of mesenchymal tumors.They originate either from the uterine smooth muscle or from the endometrial stroma. The spectrum of malignant uterine sarcomatous transformations includes leiomyosarcoma, low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), undifferentiated uterine sarcoma, and carcinosarcoma. The purpose of this study is to determine the distribution of malignant uterine sarcomatous transformations, in relation to the patient's age, epidemiological aspects, and clinical features, and to analyze the different histological types of uterine sarcomas diagnosed at our institutionand thereby to quantify their frequency and determine the most common histopathological subtype occurring in the population. Materials and methods This was a retrospective descriptive study of 21 cases of malignant uterine sarcomatous transformations, diagnosed in Saveetha Medical College, Chennai, between January 2019 and December 2022. Data was collected from the archives of the department of pathologyand from the department of medical records in the hospital. The spectrum of uterine sarcomas was analyzed in relation to the patient's age, menopausal status, presenting symptoms, preoperative diagnosis, biopsy and frozen section reports wherever available, and histopathological reports with pathological staging. Results The most common age group in which uterine sarcoma was diagnosed was found to be 61-70 years. All 10 patients who were diagnosed with carcinosarcoma were aged 60 years, andall seven patients diagnosed with low-grade endometrial stromal sarcoma were less than 50 years of age. Most of the patients were postmenopausal females, except for one patient who was premenopausal. The most common histological variety found was carcinosarcoma, malignant mixed mullerian tumor (47.6%), followed by LG-ESS (33.3%), leiomyosarcoma (14.28%), and HG-ESS (4.7%). Conclusion Uterine sarcomas are anaggressive group of tumors having a very poor prognosis. Due to its rarity and histopathological diversity, there is a lack of consensus on the risk factors.

High-Grade Endometrial Stromal Sarcoma with a Mucoid Grossly Feature: A Case Report of a 69-YearOld Iranian patient

Reporting clinical cases of high-grade endometrial stromal sarcoma tumors is essential for a better understanding of their natural course and for the development of appropriate diagnostic and treatment strategies. To date, only a few cases have been studied in this regard. In the present study, the authors present the case of a 69-year-old Iranian woman diagnosed with high-grade endometrial stromal sarcoma involving the myometrium and ovaries. The diagnosis was confirmed after pathology, which revealed myometrial and vascular involvement. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and adjuvant chemotherapy with chemotherapy regimens.

The Spectrum of Fusions Occurring in Non-Smooth Muscle Mesenchymal Uterine Tumors: A Review of the Current Knowledge.

Non-smooth muscle uterine sarcomas are mostly represented by low-grade endometrial stromal sarcoma. However, several other rare, distinct types of uterine sarcoma are recognized, including high-grade endometrial stromal sarcoma, tumors with kinase fusions, uterine tumors resembling ovarian sex cord tumors, soft tissue-type sarcoma, and emerging entities such as KAT6A/B-rearranged tumors. The landscape of uterine sarcomas has changed, mostly because of the increasing knowledge concerning their molecular aberrations. To offer a comprehensive review of the literature focusing on fusions occurring in other than smooth muscle mesenchymal uterine tumors with respect to their type, frequency, and overlap between diagnostic categories and entities. The data were mined from the PubMed/MEDLINE database covering the time period from January 1988 to June 2023. In total, 156 studies focusing on the problematics of fusions occurring in non-smooth muscle mesenchymal uterine tumors were selected, and thus became the basis for this review. One hundred ten fusions were identified in 703 tumors. The diagnostic significance of the molecular aberrations occurring in these tumors can be unclear in some cases. This can be related to the rare aberrations with a limited number of reported cases. Additionally, even well-known aberrations considered as specific for a certain distinct entity can occur in more lesions, the biological behavior and clinical significance of which can differ substantially.

A Novel EPC1 :: KDM2B Fusion in High-grade Endometrial Stromal Sarcoma.

The spectrum of endometrial stromal sarcoma (ESS) has expanded substantially since the publication of the most recent World Health Organisation (WHO) Classification of Female Genital Tumours and the advent of widely available genomic testing. We describe a uterine mesenchymal tumor harboring a novel EPC1 :: KDM2B fusion, best classified within the umbrella of high-grade endometrial stromal sarcoma (HGESS). This tumor was composed of a uniform population of spindled cells with some myxoid stroma, a mitotic rate of up to 21/10 high-power fields, and a largely pushing margin with focal vascular invasion. Immunohistochemistry showed strong and diffuse cyclin D1 positivity while CD10, WT1, DOG1, CD117, CD34, CD99, S100, MelanA, SMA, desmin, and h-caldesmon were negative. The tumor was confined to the uterus and no recurrence has been detected thus far, albeit with a short follow-up interval of 9mo.

Identification of hub genes distinguishing subtypes in endometrial stromal sarcoma through comprehensive bioinformatics analysis.

Diagnosing low-grade and high-grade endometrial stromal sarcoma (LG-ESS and HG-ESS) is a challenge. This study aimed to identify biomarkers. 22 ESS cases were analyzed using Illumina microarrays. Differentially expressed genes (DEGs) were identified via Limma. DEGs were analyzed with String and Cytoscape. Core genes were enriched with GO and KEGG, their pan-cancer implications and immune aspects were studied. 413 DEGs were found by exome sequencing, 2174 by GSE85383 microarray. 36 common genes were identified by Venn analysis, and 10 core genes including RBFOX1, PCDH7, FAT1 were selected. Core gene GO enrichment included cell adhesion, T cell proliferation, and KEGG focused on related pathways. Expression was evaluated across 34 cancers, identifying immune DEGs IGF1 and AVPR1A. Identifying the DEGs not only helps improve our understanding of LG-ESS, HG-ESS but also promises to be potential biomarkers for differential diagnosis between LG-ESS and HG-ESS and new therapeutic targets.

Endometrial stromal tumor presenting as multiple endometrial polyps with limited infiltration; a novel presentation

Abstract Introduction/Objective The 2020 WHO classifies endometrial stromal tumors into endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma, and undifferentiated sarcoma. Minimal irregularity of the interface is allowed in ESN (up to 3 foci of <3 mm). In a small number of cases, the irregular interface exceeds the acceptable criteria for ESN but relatively limited compared to most LGESS. These cases are classified as endometrial stromal tumor with limited infiltration. These tumors may recur, and it is best managed as LGESS. Methods/Case Report We report a case of endometrial stromal tumor in a 42-year-old female who presented with abnormal vaginal bleeding. Imaging showed multiple fibroids. She underwent total abdominal hysterectomy and bilateral salpingectomy. On gross examination three endometrial polyps with sharp demarcation from the adjacent myometrium were identified (largest 4 cm). Histology revealed proliferation of uniform small cells with scant cytoplasm and round to oval nuclei with rare mitotic figures in a delicate network of arterioles. Immunostains showed positive staining for CD10 and estrogen receptor while negative for Caldesmon. These polyps were mainly confined to the endometrium with only small foci of irregular border with the myometrium. No vascular invasion, high grade cytologic atypia or necrosis were seen. The tumor showed JAZF1-SUZ12 gene fusion. This case was diagnosed as an endometrial stromal tumor with limited infiltration. Results (if a Case Study enter NA) NA Conclusion In conclusion, endometrial stromal tumors are commonly submucosal or intramural, we report a rare case that presented as multiple endometrial polyps, with very limited myometrium infiltration. To our knowledge, no cases have been reported so far. It is essential to be cognizant of this entity when dealing with polypoid lesions of the endometrium, they may recur and should be managed as LGESS.

Highly malignant endometrial stromal sarcoma in a cat

An 11-year-old female Persian cat underwent ovariohysterectomy due to dilation of the uterine cavity with irregular thickening of the wall. Macroscopically, the middle and distal regions of the left uterine horn were swollen and the uterine wall was irregularly thickened due to the development of multiple coalescent, variably sized nodules. Microscopically, the nodules had originated in the endometrium and were composed of round to polygonal neoplastic cells arranged in dense sheets or ill-defined fascicles. The neoplastic cells had locally invaded the myometrium and reached the subserosa, with lymphovascular invasion. Immunohistochemically, the neoplastic cell population was partially positive for CD10, an established marker of endometrial stromal sarcoma (ESS) in humans, with focal and diffuse nuclear immunopositivity for oestrogen and progesterone receptors and immunonegativity for desmin and α-smooth muscle actin. Based on these findings, the uterine tumour was diagnosed as ESS and was considered to correspond morphologically to high-grade ESS in humans.

Pan-TRK immunohistochemistry in gynaecological mesenchymal tumours: diagnostic implications and pitfalls.

NTRK-rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a "fibrosarcoma-like" morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan-TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements. The aim of this study was to characterize pan-TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan-TRK immunohistochemistry todistinguish NTRK-rearranged sarcoma from its mimics. A total of 473 gynaecological mesenchymal tumours (461 without known NTRK fusions and 12 NTRK-rearranged sarcomas) were selected. Pan-TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan-TRK positive tumours was performed by RNA sequencing or fluorescence in situ hybridization (FISH). Of the 12 NTRK-rearranged sarcomas, 11 (92%) exhibited diffuse (≥70%) cytoplasmic pan-TRK staining with moderate/marked intensity, while the other wasnegative. Eleven (2.4%) additional tumours also exhibited pan-TRK immunohistochemical expression: three low-grade endometrial stromal sarcomas, seven high-grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of NTRK rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal/multifocal (<70%) pan-TRK cytoplasmic staining with weak/moderate intensity. Even though pan-TRK immunohistochemical expression is not entirely sensitive or specific for NTRK-rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate/strong intensity, unlike its mimics. Pan-TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and/ or S100. Ultimately, the diagnosis requires molecular confirmation.

Diagnostic des sarcomes utérins et tumeurs mésenchymateuses utérines rares à potentiel de malignité. Référentiels du Groupe Sarcome Français et des Tumeurs Rares Gynécologiques

The landscape of uterine sarcomas is becoming more complex with the description of new entities associated with recurrent driver molecular alterations. Uterine sarcomas, in analogy with soft tissue sarcomas, are distinguished into complex genomic and simple genomic sarcomas. Leiomyosarcomas and undifferentiated uterine sarcomas belong to complex genomic sarcomas group. Low-grade and high-grade endometrial stromal sarcomas, other rare tumors associated with fusion transcripts (such as NTRK, PDGFB, ALK, RET ROS1) and SMARCA4-deficient uterine sarcoma are considered simple genomic sarcomas. The most common uterine sarcoma are first leiomyosarcoma and secondly endometrial stromal sarcomas. Three different histological subtypes of leiomyosarcoma (fusiform, myxoid, epithelioid) are identified, myxoid and epithelioid leiomyosarcoma being more aggressive than fusiform leiomyosarcoma. The distinction between low-grade and high-grade endometrial stromal sarcoma is primarily morphological and immunohistochemical and the detection of fusion transcripts can help the diagnosis. Uterine PEComa is a rare tumor, which is distinguished into borderline and malignant, according to a risk assessment algorithm. Embryonal rhabdomyosarcoma of the uterine cervix is more common in children but can also occur in adult women. Embryonal rhabdomyosarcoma of the uterine cervix is almost always DICER1 mutated, unlike that of the vagina which is wild-type DICER1, and adenosarcoma which can be DICER1 mutated but with less frequency. Among the emerging entities, sarcomas associated with fusion transcripts involving the NTRK, ALK, PDGFB genes benefit from targeted therapy. The integration of molecular data with histology and clinical data allows better identification of uterine sarcomas in order to better treat them.

Next generation sequencing reveals a high prevalence of pathogenic mutations in homologous recombination DNA damage repair genes among patients with uterine sarcoma

ObjectiveInvestigate the incidence of homologous recombination DNA damage response (HR-DDR) genomic alterations among patients with uterine sarcoma. MethodsThe American Association for Cancer Research GENIE v13.0 database was accessed and patients with uterine leiomyosarcoma, adenosarcoma, undifferentiated uterine sarcoma, high-grade endometrial stromal sarcoma, low-grade endometrial stromal sarcoma, and endometrial stromal sarcoma not otherwise specified were identified. We determined the incidence of pathogenic alterations in the following genes involved in HR-DDR: ATM, ARID1A, ATRX, BAP1, BARD1, BLM, BRCA2, BRCA1, BRIP1, CHEK2, CHEK1, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, MRE11, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, WRN. Data from the OncoKB database, as provided by cBioPortal, was utilized to determine the presence of pathogenic genomic alterations. ResultsA total of 509 patients contributing with 525 samples were identified. Median patient age at sample collection was 56 years while the majority were White (80.7%). The most common histologic subtype was leiomyosarcoma (63.8%) followed by adenosarcoma (12.3%). The overall incidence of HR-DDR genomic alterations was 28.2%. The most commonly altered genes were ATRX (18.2%), BRCA2 (4%), and RAD51B (2.6%). The highest incidence of HR-DDR genomic alterations was observed among patients with leiomyosarcoma (35.4%), adenosarcoma (27%) and undifferentiated uterine sarcoma (30%), while those with low-grade endometrial stromal sarcoma had the lowest (2.9%) incidence. ConclusionsApproximately 1 in 3 patients with uterine sarcoma harbor a pathogenic alteration in HR-DDR genes. Incidence is high among patients with uterine leiomyosarcoma and adenosarcoma.

High-grade endometrial stromal sarcoma displaying immunohistochemical expression of BCOR—A report of two cases of a novel tumor entity

ABSTRACT Several defining molecular alterations have recently been identified underlying high-grade endometrial stromal sarcomas, such as YWHAE: NUTM2A/B fusions, ZC3H7B: BCOR fusions, and BCOR internal tandem duplication (ITD). BCOR is a useful immunohistochemical marker for identifying these tumors. A 37-year-old lady was presented with a 10-cm-sized tumor in the pouch of Douglas, involving the vaginal vault, bilateral adnexa, and peritoneum. A 53-year-old lady with a prior hysterectomy was presented with a 12-cm-sized tumor in the vault with abdominal deposits. Histopathological examination of both tumors revealed atypical cells comprising oval to spindle-shaped nuclei, a variable amount of myxoid stroma, and mitotic figures exceeding 10/10 high power fields. Immunohistochemically, the former tumor was diffusely positive for CD10, and the second tumor displayed patchy staining. Both tumors were positive for BCOR. Estrogen receptor (ER) showed variable staining in both tumors. By fluorescence in-situ hybridization (FISH), both tumors lacked YWHAE gene rearrangement. Both tumors had an aggressive clinical course, including extensive involvement This constitutes the first report of BCOR-positive high-grade sarcomas involving the female genital tract from our subcontinent. BCOR is a useful immunostain for identifying these relatively aggressive tumors. The differential diagnoses and the prognosis of these ultra-rare tumors are discussed herewith.

Clinical characteristics and prognostic factors of endometrial stromal sarcoma and undifferentiated uterine sarcoma confirmed by central pathologic review: A multi-institutional retrospective study from the Japanese Clinical Oncology Group

ObjectivesLow-grade and high-grade endometrial stromal sarcomas (LGESS and HGESS) and undifferentiated uterine sarcomas (UUS) are rare tumors whose pathological classification and staging system have changed recently. These tumors are reported to contain fusion genes. We aimed to clarify the genetic background, clinical features, prognostic factors, and optimal therapy of these tumors using a new classification and staging system. MethodsWe analyzed the clinical features and prognostic information of 72 patients with LGESS, 25 with HGESS, and 16 with UUS using central pathological review. Estrogen and progesterone receptors (PgRs) were examined by immunohistochemistry. JAZF1–SUZ12 and YWHAE-NUTM2A/B gene fusions were tested using real-time polymerase chain reaction. ResultsThe 5-year overall survival (OS) rates of LGESS, HGESS, and UUS were 94%, 53%, and 25%, respectively. In LGESS, stage IV, incomplete surgery, and absence of PgR were associated with poor OS. The presence of JAZF1-SUZ12 fusion gene was not associated with OS. In HGESS, the relationship between stage and prognosis was unclear. None of the 3 patients with YWHAE-NUTM2A/B fusion gene died during follow-up. Adjuvant chemotherapy was associated with a favorable OS. Incomplete resection of UUS was associated with poor OS; however, residual tumors frequently occurred. Although most patients underwent adjuvant chemotherapy, their prognosis was extremely poor even in stage I disease. ConclusionsPrognosis of LGESS is generally good; however, stage IV, incomplete surgery, and PgR-negative tumors are associated with poor prognosis. Adjuvant chemotherapy may be useful for HGESS. Prognosis of UUS is extremely poor, even with adjuvant chemotherapy.

Prognostic factors, oncological treatment and outcomes of uterine sarcoma: 10 years’ clinical experience from a tertiary care center in Pakistan

BackgroundUterine sarcoma is an uncommon aggressive malignancy. Optimal management and prognostic factors have yet to be well recognized due to their rarity and various histological subtypes. This study aims to investigate these patients' prognostic factors, treatment modalities, and oncological outcomes.MethodsA single-center retrospective cohort study was conducted on all patients diagnosed with uterine sarcoma and treated from January 2010 to December 2019 in a tertiary-care hospital in Pakistan. The data were analyzed using STATA software and stratified on the histological subtype. Survival rates were estimated using the Kaplan–Meier method. Crude and adjusted hazard ratios with 95% CI were estimated using univariate and multivariate analysis.ResultsOf the 40 patients, 16(40%) had uterine leiomyosarcoma (u-LMS), 10(25%) had high-grade endometrial stromal sarcoma (HGESS), 8(20%) had low-grade endometrial stromal sarcoma (LGESS) and 6(15%) had other histological subtypes. The median age of all patients was 49 (40–55.5). Thirty-seven (92.5%) patients underwent primary surgical resection, and 24 (60%) patients received adjuvant systemic chemotherapy. The survival plots showed the overall population's DFS of 64 months and the OS of 88 months (p-value = 0.001). The median DFS in all patients was 12 months, and the median OS was 14 months (p-value = 0.001). A small but significant DFS benefit was found in patients who received adjuvant systemic chemotherapy, 13.5 versus 11 months (p-value = 0.001). Multivariate Cox-regression analysis revealed that large tumor size and advanced FIGO stage were substantial factors associated with decreased survival.ConclusionUterine sarcomas are rare malignancies with poor prognosis. Multiple factors, including tumor size, mitotic count, stage of the disease, and myometrial invasion, impact survival outcomes. Adjuvant treatment may decrease the recurrence rate and improve DFS but do not affect OS.

ASSESSMENT OF PROLIFERATIVE ACTIVITY OF ENDOMETRIAL STROMAL TUMORS USING AgNOR TECHNOLOGY

Endometrial stromal sarcomas (ESS) are rare neoplasms that arise from the endometrial stroma and account for less than 1% of all uterine malignancies. Diagnosis of ESS can be challenging due to its morphological overlap with other endometrial tumors, such as endometrial stromal nodules and stromal endometriosis. AgNOR count is a marker of cell proliferation and has been proposed as a potential tool for differentiating between different types of endometrial tumors.In this study, we analyzed the AgNOR count in 50 cases of endometrial tumors, including endometrial stromal nodules, stromal endometriosis, low-grade ESS, and high-grade ESS. Our results show that there is a significant difference in the AgNOR count across different types of endometrial tumors, with the mean AgNOR count increasing with the severity of the tumor. Endometrial stromal nodules had the lowest mean AgNOR count, while high-grade ESS had the highest.These findings suggest that AgNOR count may be a useful marker for differentiating between different types of endometrial tumors, including ESS. However, further research will be needed to confirm these findings and explore the clinical utility of this marker in the diagnosis and management of these conditions. Overall, our study contributes to our understanding of the biology of endometrial tumors and provides valuable information that may be useful in the development of diagnostic and treatment strategies for these conditions.